Regorafenib in Bone Sarcoma: A Systematic Review and Meta-Analysis of Its Effectiveness and Safety in Cancer Treatment

ObjectivesBone sarcomas are aggressive malignancies with limited treatment options in advanced stages. Regorafenib, an oral multi-kinase inhibitor, has showed potential efficacy in early-phase trials. However, its overall effectiveness and safety profile in bone sarcoma remain unclear. This systematic review and meta-analysis aim to assess the clinical impact of regorafenib on survival outcomes and adverse events in patients with bone sarcomas. MethodsA systematic search was conducted across PubMed, Web of Science, and Scopus for randomized controlled trials (RCTs) published between September 27, 2012, and April 2024. Eligible studies included full-text RCTs comparing regorafenib to placebo in the treatment of bone sarcomas. Meta-analyses, reviews, case reports, conference abstracts, ongoing trials, and animal studies were excluded from the analysis. The primary endpoints were progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Data synthesis was performed using a random-effects model, and heterogeneity was assessed via the I{superscript 2} statistic. The Cochrane Risk of Bias tool (RoB 2) was applied to evaluate study quality. Statistical analysis was conducted using R version 4.3.1. ResultsA total of five RCTs met the inclusion criteria. Regorafenib significantly improved PFS compared to placebo (MD = 9.69 weeks; 95% CI: 4.54, 14.84; I{superscript 2} = 0%), while no statistically significant improvement was observed in OS (MD = 0.85 weeks; 95% CI:-36.33, 38.02; I{superscript 2} = 0%). Predominantly observed treatment-emergent effects linked to regorafenib included hand-foot skin reaction, hypertension, asthenia or fatigue, and diarrhea. ConclusionRegorafenib significantly improves progression-free survival in bone sarcoma but does not show a clear benefit in overall survival. While adverse events are common, they are generally manageable. Further research is needed to optimize dosing, patient selection, and to determine the long-term survival benefits.